First Time in Human Study (FTIH) With Positron Emission Tomography (PET)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
|Official Title:||A Single-blind, Randomised, Placebo-controlled, Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK1144814 in Healthy Male and Female Subjects and an Open-label Positron Emission Tomography Study in Healthy Male Subjects to Evaluate the Neurokinin-1 (NK1) Receptor Occupancy of GSK1144814 in the Living Human Brain Using 11C GR205171.|
- Safety and tolerability: Adverse event monitoring, vital signs (blood pressure, heart rate, respiratory rate, oral body temperature, ECGs (12 lead and Holter), clinical laboratory assessments (standard laboratory parameters). [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
- Pharmacokinetics: time-point immediately prior to the first quantifiable plasma concentration (tlag), Cmax, time of occurrence of Cmax (tmax), AUC from time zero (pre dose) to the time of the last quantifiable concentration (AUC0-infinity), [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
- Volume of distribution (VT) of [11C] GR205171 in the brain at Baseline and following oral doses of GSK1144814. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
- NK1 receptor occupancy in the brain at Baseline and following oral doses of GSK1144814. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
|Study Start Date:||October 2008|
|Study Completion Date:||April 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Experimental: Part A, Cohort 1
In Cohort 1, four subjects (two on active and two on placebo for first dose, and then three on active and one on placebo for subsequent doses) will be included. Subjects will be dosed at least 30 minutes apart over the dosing day and only doses administered where the predicted plasma concentration will remain below those corresponding to the MABEL.
Experimental: Part A, cohort 2
In Cohort 2, 10 subjects will be included (8 active : 2 placebo). Dosing will start once the previous cohort (Cohort 1) has completed the Treatment Phase. For Cohort 2 and any subsequent cohorts, dosing will take place on two different days when a new dose is administered such that no more than one subject receives the agreed ascending dose on the first dosing day. Doses may be split in up to three divided doses given 2 to 3 hours apart. Dosing for the first four sessions in each cohort will be staggered over 2 days. On the first day of each dosing session, only one subject will receive the highest dose for that dosing session and at least one subject each will receive placebo. The remaining subjects in the cohort will be dosed on the second day according to the randomisation plan.
Single dose which may be split in up to three divided doses given 2 to 3 hours apart.
Experimental: Part B
Part B of the study will consist of a Screening Visit (up to 30 days before the dosing session), three PET scans (where possible, all three scans may be performed in one visit when subject is admitted overnight) and a Follow-up Visit. Each subject will receive an oral dose of study drug. The dose may be split in up to three divided doses given 2 to 3 hours apart.
Single dose that may be split in up to three divided doses given 2 to 3 hours apart.
GSK1144814 is a dual neurokinin-1 (NK1) and neurokinin-3 (NK3) antagonist with the potential to treat schizophrenia & depression.
This study described in the present protocol consists of two sections. Part A is the first administration into man to evaluate the safety, tolerability and pharmacokinetics of single ascending doses of GSK1144814. The study is a single-blind, randomised, placebo-controlled design in healthy male and female (of non-childbearing potential) subjects. Part B will be an open-label design in healthy male subjects to assess the GSK1144814 NK1 receptor occupancy by positron emission tomography (PET) scanning with [11C]-GR205171.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01381419
|GSK Investigational Site|
|Harrow, Middlesex, United Kingdom, HA1 3UJ|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|